This invention relates generally to catheters for use in delivery of drug, particularly in the context of site-specific drug delivery.
Delivery of drug to a specific treatment site represents a substantial challenge in the design of drug delivery systems. Site-specific drug delivery can be particularly challenging when the drug is to be delivered long-term (e.g., several hours to several days, weeks, or months). One approach to accomplish site-specific drug delivery involves the use of a catheter, which can be positioned at a treatment site to facilitate localized delivery of drug from a drug reservoir that may be some distance from the treatment site. Long-term drug delivery requires that such catheters be biocompatible, drug non-reactive, impermeable, and flexible (e.g., not sharp or easily breakable while implanted in the body).
The combination of required characteristics of drug delivery catheters limits the materials available for their design. For example, while a variety of biocompatible materials have sufficient flexibility, these materials may not have the required impermeability and drug non-reactive characteristics. Similarly, while many materials may be both drug non-reactive and impermeable, they may not be sufficiently biocompatible and flexible.
The problem is further complicated where it is desirable to deliver drug in relatively small amounts, and thus requires a small drug delivery lumen. Catheters having a small inner lumen for drug delivery are often extremely difficult to handle due to, for example, their fragility and their small outer diameters. Adapting a catheter having a larger outer diameter to have a smaller inner lumen can provide a catheter that is handleable, but too stiff for implantation through tortuous bends in the implantation pathway that leads to the treatment site.
There is thus a need in the field for a drug delivery catheter that is biocompatible, flexible, handleable (even when designed for delivery of microquantities of drug), and sufficiently impermeable and drug non-reactive. The present invention addresses these problems.
The present invention features a composite catheter comprising an elongate outer member and an elongate inner member positioned within the outer member so that the inner and outer members define an interstitial space. The outer member has a size and other characteristics that facilitate handling and implantation of the composite catheter, while the inner diameter of the inner member has the size and other characteristics suitable for delivery of a drug through a lumen of the inner member. The interstitial space imparts flexibility to the composite catheter by, for example, removing material from the cross-sectional area that would otherwise provide additional stiffness to the catheter, and/or by accommodating movement of the outer member relative to the inner member.
In one aspect the invention features a catheter comprising an elongate outer member and an elongate inner member, where the inner member is positioned within a lumen defined by the outer member so as to define an interstitial space between an outer wall of the inner member and an inner wall of the outer member, and where a lumen defined by the inner member is suitable for delivery of drug at a low volume rate. In specific embodiments the catheter further comprises a support member positioned within the interstitial space.
In one embodiment, the catheter of the invention comprises a flexible distal portion. The flexible distal portion can be provided as an extension of a distal end of the outer member beyond the inner member distal end, or as an additional component attached to the distal end of the catheter. The flexible distal portion is flexible relative to a portion of the catheter comprising the outer member and the inner member.
In specific embodiments, the distal extension is substantially hollow, and the inner member lumen and a lumen defined by the flexible distal portion form a drug delivery conduit. In other specific embodiments, the drug delivery outlet is defined by an opening at a distal end of the flexible distal portion. In still other specific embodiments, the drug delivery outlet is defined in a sidewall of the flexible distal portion, or the inner member lumen terminates in a drug delivery outlet at a sidewall of the catheter proximal to the flexible distal portion.
In another aspect the invention features a drug delivery system comprising a drug delivery device and a composite catheter of the invention.
In another aspect the invention features a method for low volume rate delivery of a drug to a treatment site in a subject comprising the steps of: 1) implanting a catheter of the invention into a subject to provide a drug delivery pathway from a proximal end of the catheter, through a lumen defined by a catheter inner member to a distal end of the catheter, and out a drug delivery outlet positioned at a treatment site in a subject; and 2) introducing a drug into the inner lumen of the catheter to deliver drug to the treatment site in the subject.
A primary object of the invention is to provide a catheter useful in accurate and reliable delivery of very small volume of a drug, e.g., microliter quantities of a liquid or semisolid drug formulation, which catheter is biocompatible, flexible, and readily handleable to facilitate implantation.
Another object of the invention is to provide a catheter that can be used with a variety of drug delivery systems to accomplish site-specific drug delivery.
It is another object of the invention to provide a catheter that is suitable for delivery of drug to a distal treatment site within a subject, particularly sites that are highly sensitive or fragile (e.g., the spinal cord).
An important advantage of the invention is that the interstitial space defined by the inner wall of the outer member and the outer wall of the inner member accommodates movement of the outer and inner members relative to one another, e.g., in a plane perpendicular to a sidewall of the catheter, and further can make the catheter less stiff by removing material from the catheter cross-sectional area. Furthermore, the interstitial space can be designed to provide for varying degrees of flexibility of the catheter, e.g., by varying the dimensions of the space (e.g., the distance between the outer member inner wall and the inner member outer wall). The interstitial space can also be designed to accommodate other desirable catheter elements. For example, the space can be designed to accommodate one or more support members, which support members can enhance the tensile strength or compression strength of the composite catheter. In addition or alternatively, desirable characteristics can be imparted to the catheter by filling the interstitial space with a gas, liquid, semi-solid, or polymer (including cross-linked polymers) that is under substantially constant or regulatable pressure, and that optionally comprise antimicrobial (e.g., bacteriostatic or bactericidal) agents.
Another important advantage of the invention is that the composite catheter facilitates delivery of extremely small volumes of drug (e.g., submicroliter volumes), yet is easily handled, e.g., by a clinician during implantation. This advantage of the catheter is provided by the combined characteristics of the inner member, which provides the drug delivery conduit, and the outer member, which provides for the biocompatibility and ease of handling of the composite catheter. Furthermore, by facilitating delivery of small volumes of drug, the catheter reduces the economic costs as well as the risks associated with systemic dosing.
Another advantage of the invention is that the material used for the outer member need not be drug impermeable, since at most only the inner member need be substantially drug impermeable. Thus any available biocompatible and implantable grade material (e.g., silicone rubber) can be used for the outer member. Thus the catheter can take advantage of a wider range of biocompatible materials for the outer member than can conventional catheters in which the material of the outer catheter wall is in contact with the drug formulation to be delivered.
Another advantage of the invention is that the catheter inner member and the catheter outer member can have distinctly different characteristics in terms of, for example, relative flexibility, dimensions, biocompatibility, etc, which characteristics can be varied and selected according to any of a variety of factors, e.g., the drug to be delivered, the desired flow rate, the treatment site, etc. For example, the material of the outer member can be selected to provide for biocompatibility, size, flexibility, and other catheter characteristics important for implantation and retention in the subject without significant constraint imposed by the properties important for delivery of drugs, while the inner member of the composite catheter can be selected to provide the size, non-permeability to drug, non-reactivity to drug, and other characteristics optimal for delivery of drug without significant constraint imposed by biocompatibility, flexibility, and other characteristics important to handling and implantation in a subject. This combination allows for use of a wider variety of materials in the manufacture of the drug delivery conduit defined by the inner member since the outer member will protect the subject from the inner member material, e.g., the inner member may comprise materials that would be too sharp, stiff, or otherwise unsuitable for implanting in a subject. Similarly, the outer member can be provided in dimensions that facilitate ease of handling and implantation, while the inner member can be of relatively smaller dimensions, e.g., to define an extremely small inner lumen for delivery of drug at a relatively low volume rate. In addition, the use of the outer and inner member allows for more design flexibility, e.g., varying the inner and outer diameters to provide dimensions suitable for drug delivery and handleability, respectively; varying the materials for the outer member and the inner member to provide for biocompatibility and drug-impermeability, respectively; etc.
The invention is also advantageous in that the inner lumen of the inner member can be designed to provide a drug delivery conduit with a small lumen size to, for example, minimize start-up time, i.e., the time for delivery of drug from a drug reservoir of a drug release device, through the catheter, and to the treatment site.
Still another advantage of the invention is that the catheter can be designed to have an extremely floppy (flexible) distal portion that can serve as a means for anchoring the catheter at a treatment site, and can be cut to a desired length by the clinician to provide for tailoring the catheter to the present needs of the subject and/or treatment site. Furthermore, the drug delivery outlet can be positioned within a sidewall of the catheter to provide for delivery of drug at or about the anchoring point at a treatment site (e.g., at or about the point at which the floppy distal portion begins, see, e.g., FIGS. 9-11).
These and other objects, advantages and features of the present invention will become apparent to those skilled in the art upon reading this disclosure in combination with drawings wherein like numerals refer to like components throughout.